RT Journal Article
SR Electronic
T1 Alpha 1 Antitrypsin is an Inhibitor of the SARS-CoV2–Priming Protease TMPRSS2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.04.077826
DO 10.1101/2020.05.04.077826
A1 Nurit P. Azouz
A1 Andrea M. Klingler
A1 Marc E. Rothenberg
YR 2020
UL http://biorxiv.org/content/early/2020/05/05/2020.05.04.077826.abstract
AB The transmembrane serine protease TMPRSS2 is indispensable for S protein priming of the MERS, SARS-CoV, and SARS-CoV2 coronaviruses, a process that is necessary for entry of the virus into host cells. Therefore, inhibiting TMPRSS2 holds promise as an approach toward preventing transmission of coronaviruses. Herein, we developed an in vitro system to measure TMPRSS2 activity and tested the inhibition of TMPRSS2 by several synthetic and natural protease inhibitors. Camostat mesylate and bromhexine hydrochloride (BHH) inhibited TMPRSS2 proteolytic function. In addition, we identified the small molecule 4-(2-aminomethyl)benzenesulfonyl fluoride (AEBSF) and the human, anti-inflammatory protein alpha 1 antitrypsin (A1AT) as inhibitors of TMPRSS2. AEBSF and A1AT inhibited TMPRSS2 activity in a dose-dependent manner. AEBSF and A1AT inhibited TMPRSS2 in the same range of concentrations (100-0.1 μM). We suggest that treatment with these inhibitors, particularly A1AT, which is an FDA-approved drug, might be effective in limiting SARS-CoV and SARS-CoV2 transmissibility and as a COVID-19 treatment.Competing Interest StatementThe authors have declared no competing interest.